The aim of this project is to delineate biochemical mechanisms of vasocative hormones, e.g., prostaglandins, catecholamines, angiotensins and vasopressin, in cardiovascular and renal systems. (A) Prostaglandin E2, angiotensin II and other hormones have been shown to affect glomerular dynamics; and it has been postulated that effects of these hormones in the glomerular may be mediated through cyclic AMP. However, the anatomical origin of prostaglandin E2-dependent cyclic AMP in the kidney is not known. During the last year, this laboratory has demonstrated that prostaglandin E2 stimulates cyclic AMP generation in the isolated glomeruli, but not in tubules; and that angiotensin II, which is known to be antagonistic to the effect of prostaglandin E2 on glomerular dynamics, partially inhibited prostaglandin E2-dependent cyclic AMP generation in the glomerulus, supporting the postulate that certain effects of prostaglandin E2 on glomerular functions may be mediated through cyclic AMP, and that angiotensin II may attenuate the effect of prostaglandin E2 on glomerular dynamics at the step of cyclic AMP generation. (B) The effect of prostaglandin E2 on cyclic AMP generation in the kidney was investigated in vivo by measuring urinary cyclic AMP excretion. Stimulation of nephrogenous prostaglandin E2 release by furosemide or ethacrynic acid administration (which had been shown by other investigators) increases urinary cyclic AMP excretion. This increase in cyclic AMP excretion was independent of increases in urinary flow rate, sodium excretion or free water clearance; and suppression of prostaglandin synthesis by Indomethacin decreased cyclic AMP excretion, suggesting that nephrogenous prostaglandin E2 stimulates cyclic AMP generation in the kidney in vivo.